Saint Louis University

University of Kansas

The City University of New York

Lynda Anne Morrison

John Edwin Tavis

Marvin Jay Meyers

David J Davido

Ryan Murelli

Lydia G Thebeau

Jane E Schrimpf

The present disclosure relates to inhibitors of herpesvirus nucleic acid metabolism and inhibitors of Hepatitis B virus. Also provided are methods of treatment using these agents.

Hydroxylated tropolone inhibitors of nucleotidyl transferases in herpesvirus and Hepatitis B and uses therefor

The present disclosure relates to identification of inhibitors of hepatitis and herpesvirus replication including compounds of the formula: wherein the variables are as defined herein. Also provided are methods of treatment using agents so identified.

Inhibitors of nucleotidyl transferases and uses in herpes and hepatitis viral infections therefor

The present invention involves identification of inhibitors of herpesvirus nucleic acid metabolism. Also provided are methods of treatment using agents identified.

Inhibitors of HSV nucleotidyl transferases and uses therefor

A mutant HSV-1 (referred to herein as KOS-NA) was generated. KOS-NA contains novel mutations in the UL39 gene, which encodes for a protein that is a large subunit of ribonucleotide reductase (i.e., ICP6). These UL39 mutations were found to alter two amino acids in ICP6 (R950H and L393P) and are responsible for attenuation of KOS-NA in vivo, and resulted in diminished ICP6 protein levels. These novel UL39 mutations regulate the expression and/or stability of ICP6 and severely impact HSV-1 pathogenesis. Mutant HSV viruses containing these mutations appear to protect against HSV infection and can serve as therapeutic vaccines to help combat preexisting HSV infection in infected individuals.

Neuroattenuated herpes simplex virus

An antiviral vaccine that encodes costimulation molecules for increasing immune response to the particular virus at issue is provided herein. In an illustrative embodiment, in mice lacking both B7-1 and B7-2 (B7KO), the increased severity of HSV infection has confirmed the importance of these molecules in generation of HSV-specific immunity. To test the concept that B7-1 or B7-2 expression by replication-defective HSV could augment its immunogenicity and protective capacity, the present inventors constructed replication-defective HSV-2 encoding B7-1 or B7-2. Both viruses partially reconstituted immune responses to HSV compared with replication-defective virus alone when used to immunize B7KO mice, indicating that the increased responsiveness to virus could be attributed to virus-encoded B7 molecules.

Growing community of inventors

Webster Groves, MO, United States of America

Lynda Anne Morrison